A large number of hormones and neurotransmitters are regulating the functions of the living body through specific receptors present in the cell membrane. Many of these receptors perform intracellular signal transduction through the activation of guanine nucleotide-binding proteins (hereinafter, sometimes abbreviated to “G proteins”) to which they are coupled. Since these receptors have a common structure with seven transmembrane domains, they are called G protein-coupled receptors or seven times transmembrane type receptors (7TMRs).
The hypothalamus-pituitary system is one of those passways which the above-mentioned hormones/neurotransritters and G protein-coupled receptors regulate the functions of the living body. The secretion of pituitary hormones from the pituitary is regulated by hypothalamic hormones, and the functions of target cells/organs are regulated through pituitary hormones released into the blood. The regulation of functions important for the living body, such as the maintenance of homeostasis, development of the reproductive system or individuals, regulation of metabolism or growth, and so forth is performed through this passway.
The secretion of pituitary hormones is regulated by positive or negative feedback mechanisms involving hypothalamic hormones and peripheral hormones secreted from target internal secretion glands.
It is known that these hormones, factors and their receptors are not localized in the hypothalamus-pituitary system but, in general, distributed widely in the brain. Therefore, it is considered that substances called hypothalamic hormones are functioning as neurotransmitters or neuromodulators in the central nervous system.
These hormones, factors and their receptors are distributed similarly in peripheral tissues, and are considered to have important functions individually.
Under circumstances, development of medicines that regulate the secretion of pituitary hormones from the pituitary through regulation of functions of the living body by a G protein-coupled receptor and its ligand, particularly through regulation of hypothalamic hormone secretion, has been desired.
A peptide that regulates prolactin release is disclosed in Nature Cell Biology, Vol. 2, October 2000, pp. 703–708.
Secretory peptides designated RFRP-1, RFRP-2 and RFRP-3, and a G protein-coupled receptor protein OT7T022 to which these peptides bind are disclosed in WO 00/29441.
It is disclosed in WO 01/66134 that those secretory peptides have an effect in regulating prolactin secretion.
It is an object of the present invention to provide a novel polypeptide which has an excellent effect in regulating release.